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March 7th, 2025
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Kyungpook National Univerity
molecular biology
biorxiv

Novel DNA endonuclease activity of human ERK1 protein

Ju, S.Open in Google Scholar•Jeong, J.Open in Google Scholar•Joo, B. C.Open in Google Scholar•Lee, S. J.Open in Google Scholar•Tarassov, S.Open in Google Scholar•Chang, J. H.Open in Google Scholar•Jeon, J. H.Open in Google Scholar•Calderwood, S. K.Open in Google Scholar•Lee, Y. U.Open in Google Scholar•Bunch, H.Open in Google Scholar

ERK1 is a key kinase in the mitogen-activated protein kinase pathway, which transduces extracellular signals into cellular responses. Following triggering of the pathway, cytosolic ERK1 is phosphorylated and translocated into the nucleus to activate DNA-bound factors and target genes. This study reports a novel role of human ERK1 as a DNA endonuclease to catalyze single-strand DNA breaks without sequence-specificity. ERK1 catalysis required magnesium ion and was independent of ATP. Biochemical and structural analyses indicated that the ERK1 N-terminal domain allosterically modulates substrate binding and catalytic rate. Fluorescence imaging showed that ERK1 interacts with cytoplasmic DNAs in condensates. Collectively, our study reveals an unprecedented role of ERK1 in breaking DNA molecules, a finding which highlights the potential of ERK1 to regulate cytoplasmic DNA topology and fate.

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